This protocol compares diabetes (DM) and heart disease risk in African-Americans (AA) and African immigrants. The AA cohort is known as TARA for: Triglyceride and Cardiovascular Risk in AA. The African immigrants are known as the: Africans in America cohort. The sample of AA participating is representative of the AA population in the US because the prevalence of obesity (43%), pre-diabetes (preDM) (22%) and hypertension (21%) is similar to National Health and Nutrition Examination Survey data. However, there is no national data on diabetic or cardiac health of African immigrants. Therefore we are working to establish a database. To determine the prevalence of DM and preDM, we are relying not just on fasting glucose but we are also performing oral glucose tolerance tests and measuring A1C levels and glycated albumin levels. In performing these tests, we discovered that the prevalence of preDM and hypertension is twice as high in African than AA men. In addition the rate of undiagnosed DM was 7% in African men vs <1% in AA men. In contrast the rate of hypertension, DM and preDM are similar in African and AA women. Identifying the reasons for why African immigrant men are less healthy than AA men is a major focus of research in this protocol. To improve the metabolic health of African men, it is essential to learn why preDM, DM and hypertension is occurring more often in African men than AA men even though African men are less obese, less likely to be smokers and more likely to be married. As a next step we are examining the effect of stress of immigration on the health of African immigrants. We are measuring cardiometabolic stress with the Allostatic Load Score. The specific immigration related factors we are examining are: age of immigration, duration of stay in the US and reason for immigration. We have discovered that when the reasons for immigration are work, study or asylum/refugee, the degree of stress is higher than when the reasons for immigration are associated with keeping families together through reunification programs, marriage or diversity lottery for self and immediate family. Hence reason for immigration is key medical history. In addition, we are studying if A1C as a diagnostic test for DM, can replace the oral glucose tolerance test in people of African descent. A1C is a hemoglobin dependent test and African immigrants have a high prevalence of sickle cell trait (SCT) (i.e. 10 to 40%) and hemoglobin C (HbC) trait (i.e. 15% in West Africa). Therefore before widespread use of A1C as a diagnostic test for DM is instituted in Africa, validation is necessary. When we evaluated diagnostic efficacy of A1C in African immigrants, we found that the sensitivity was 50%. When the Africans are divided according to SCT status, the sensitivity of A1C was 50% in both groups. Therefore, A1C is not be an ideal test in Africans and SCT may not be a compromising factor. However we have data on the effect of HbC trait on the diagnostic efficacy of A1C. We found in the small sample number of African immigrants with HbC trait, that the diagnostic efficacy was < 20%. We believe we are the first to study the influence of HbC trait on the diagnostic efficacy of A1C. Most studies either exclude people with HbC trait from analyses or combine them with people with sickle cell trait. Therefore the effect of HbC trait is not detectable. We need a larger sample size of people HbC trait in order to definitive prove whether HbC trait represents yet another reason why A1C is a suboptimal diagnostic test in Africans. Glucose 6 phosphate dehydrogenase (G6PD) deficiency is another factor that might affect the diagnostic efficacy of A1C. G6PD deficiency is more common in African than European descent populations. A recent GWAS analyses predicted that G6PD deficiency is associated with A1C levels that are 1% lower than in the absence of G6PD deficiency. If this is true, it would be another factor lowering the efficacy of A1C as a diagnostic test in African descent populations. This GWAS study needs to confirmed or disapproved with actual metabolic data and we have just begun to collect that data. To achieve better efficacy, we are in the process of examining alternatives such as glycated albumin as a single test and in combination with A1C. We have found that fasting glucose combined with A1C has a diagnostic sensitivity of 70%. But since obtaining a fasting sample can be problematic, we tested the combination of A1C and glycated albumin. We have found that in the detection of DM and preDM, the combination of A1C and glycated albumin had a diagnostic sensitivity of 72%. This is important because glycated albumin is an inexpensive, easy test to set up and run. We have established a collaborations with a physician in Nigeria to directly evaluate the efficacy of A1C and glycated albumin. The relationship of body size to cardiovascular and DM risk is another area of investigation. In our cohorts, the mean body mass index (BMI) in AA is 30.6 kg/m2 but only 26.4 kg/m2 in African immigrants. BMI is a mathematical method used to correct weight for height. Due to the broad range of BMI in the participants in this cohort, it is possible to evaluate the relationship of body size to insulin resistance, a major factor in the development of DM, and heart disease. We have found in AA men a waist circumference (WC) of 102 cm predicts both insulin resistance and obesity. This is in agreement with the National Cholesterol Education Program values for whites. But in African men, insulin resistance occurs at a much lower WC, specifically 91 cm. This difference between AA and African immigrant men, suggests that a single WC of risk does not apply to all African descent populations. In AA women we found that a WC of 96 cm predicted both insulin resistance and obesity and this WC of risk was similar in AA, African immigrant, Black South African and West African women. Therefore among populations of African descent, there may be less variation in women than men. However, as the WC of risk is 88 cm in white women, there is a large difference by race. Guidelines which screen for disease might be more effective if this was better appreciated and more fully understood. Elevated TG and low HDL are considered lipid hallmarks of insulin resistance. However while elevated TG is a marker of insulin resistance in whites, we have shown that TG is not a marker of insulin resistance in AA. Results from TARA were so impressive that the hypothesis that TG was not a marker of insulin resistance in African Americans was subsequently tested in NHANES data collected from 1999-2001. In this NHANES data set of whites, AA and Mexican Americans, the fact that TG was not a marker of insulin resistance was confirmed. However, TG was a powerful marker of insulin resistance in whites and Mexican Americans. Altogether this research on race differences in the relationship of TG to insulin resistance again demonstrates that to detect disease at time when intervention can affect outcome, there is a need to develop ethnic-specific guidelines. Recently the TG/HDL ratio at a level of >3.0 has been suggested to be a marker of insulin resistance. This is well established in whites. After demonstrating the TG/HDL ratio did not work in AA, we tested the ratio in white South African women, Black South African women and West African women. While the ratio effectively predicted insulin resistance in the white women, it did not work in any group of African descent women of African. Hence findings related to insulin resistance in whites are not universally applicable. In summary this protocol is dedicated to undertaking research which defines relevant risk factors, prevents through early diagnosis, DM and heart disease in people of African descent globally.